Nanoparticles mimic the natural bone formation environment – synthesis

Ceramic materials based on calcium phosphate (CaP) are widely used for the repair and regeneration of bone tissue. Applications in fractures and bone loss are caused, for example, by operations to remove tumors or diseases such as osteoporosis. Commercially available synthetic ceramics today work beneath natural tissue taken from the patient or from tissue banks.

Therefore, a synthetically reproducible composition, structure and thus biological function of the materials are sought that are responsible for bone formation and regeneration in the human body and other living organisms. Researchers at the Physical and Chemical Laboratory for Surfaces and Colloids on the Ribeirão Preto Campus of the University of São Paulo (USP) have just achieved important results in this regard, with the synthesis of calcium and strontium phosphate nanoparticles similar to the structures present in our bodies .

The shell of a mollusk such as mussel or scallop and school chalk consist of the same material, the mineral calcium carbonate (CaCO3). However, as we all know, it is easy to turn chalk into powder with just one hand, while mussels are known for their mechanical strength.

Responsible for this difference is biomineralization, in which living organisms in the presence of organic macromolecules produce minerals from chemical elements that have been removed from the environment. This is how our bones and teeth are built up, and mistakes in this process, in turn, lead to osteoporosis.

“What sets biomineralization apart is the fact that it is an extremely regulated process. Our bones don’t grow anywhere in places controlled by a matrix, ”says Camila Bussola Tovani, member of the USP group. “The process enchants scientists because it is chemically simple, but leads to highly developed structures, the complexity of which humans still cannot reproduce in the laboratory,” he said.

“The inorganic part of our bones consists of the mineral apatite, a calcium phosphate that we can produce on the laboratory bench as hydroxyapatite. However, the bio-mineralized apatite in the human body from an organic collagen matrix has very different properties, in particular mechanical resistance, ”adds Ana Paula Ramos, who led Tovani’s doctoral thesis.

In order to produce the nanoparticles, the researchers sought inspiration precisely from the natural production conditions of our bones and teeth.

Bone regeneration processes are constantly taking place in our body. In them, the basic unit, a kind of mold in which biomineralization takes place, is the collagen fibrils, a cylindrical organic matrix in which the formation of calcium phosphate crystals takes place in a very small space and thus leads to structures with shape and size controlled and well defined.

To mimic this cylindrical shape, a commercially available polymeric polycarbonate membrane with pores with uniform dimensions of about 200 nanometers in diameter was similar in size to the fibrils. The membrane was immersed in a solution containing phosphate, calcium and strontium, an element known to act in the regeneration and control of bone tissue loss.

After the solution has penetrated the membrane pores, drying is carried out in the presence of compounds that provoke mineralization. The polycarbonate is then dissolved, leaving the cylindrical nanoparticles of calcium and strontium phosphate behind.

When analyzing these nanoparticles in a culture of osteoblasts (cells that are responsible for the formation of bone tissue) in the laboratory, the research group checked their activity in tissue regeneration. “The material is not only structurally and morphologically similar to the original bone matrix, but also locally supplies strontium ions that regulate the activity of important cells in the bone formation process,” explains Ramos.

The cells mentioned are osteoclasts, which are responsible for the reabsorption of bone tissue and whose activity is increased in people with osteoporosis. The combination of route mineralized calcium phosphate, which mimics the natural process of strontium ions, has thus led to the combination of the ability to induce biomineralization and control the activity of osteoclasts that cause the loss of density of bone tissue through reabsorption.

The researchers say the next steps will be tests with nanoparticles, which will be applied in polymer matrices used in repairing serious defects, which will be added to toothpastes to treat dentin hypersensitivity. “The particle as it is, as a compacted powder, could already be used to repair small defects, such as in an orthodontic implant. The matrices of other materials are used in grafts that require support, such as in the tibia, ”explains Ramos.

Another challenge is building partnerships for studies on animal models and later on humans. “Science is not done alone. We are physicochemical and we would not be able to use the nanoparticles that we produce during bone regeneration if we did not work with biochemical colleagues, doctors and pharmacists, ”emphasizes the professor at the USP. “In addition, the impact of the results achieved shows the importance of investing in the internationalization of Brazilian research, as it was only possible because of the partnerships we have established with institutions in France,” he concludes, reporting that Tovani during his PhD has completed an internship at the Sorbonne. where she is now working as a postdoc.

Electron microscope image of nanoparticles that were synthesized by the research group

Electron microscope image of nanoparticles that were synthesized by the research group. On a black background, the gray-appearing nanoparticles form a kind of fabric, with the fibers arranged horizontally.

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